Studies will be directed toward elucidation of the mechanisms by which x-rays alter the proliferation of mammalian cells, with special emphasis on the molecular events leading to cell death. Synchronous cultures of various cell lines will be irradiated with lethal doses of 220 kV x-rays, and DNA synthesis will be examined in both the irradiated and the succeeding generations. Depression in rate and/or amount of replication will be analyzed in terms of replicon initiation and completion. Cells undergoing permanent mitotic arrest will be examined for structural and biochemical abnormalities. The relation between these and deficient DNA synthesis will be sought. The existence and role of RNA damage in lethally irradiated cells will be examined. Cells bearing potentially lethal radiation damage will be exposed to agents that promote expression of that damage and examined for aberrant DNA synthesis.